EIS_MYCTU
ID EIS_MYCTU Reviewed; 402 AA.
AC P9WFK7; L0TCA0; P71727; Q9RG79;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2017, sequence version 2.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=N-acetyltransferase Eis {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:19906990, ECO:0000269|PubMed:21628583, ECO:0000269|PubMed:22547814};
DE AltName: Full=Aminoglycoside N-acetyltransferase {ECO:0000303|PubMed:19906990, ECO:0000303|PubMed:21628583};
DE AltName: Full=Enhanced intracellular survival protein {ECO:0000303|PubMed:10629183, ECO:0000303|PubMed:17449476};
DE AltName: Full=Protein-lysine N-acetyltransferase {ECO:0000305|PubMed:22547814};
GN Name=eis {ECO:0000303|PubMed:10629183}; OrderedLocusNames=Rv2416c;
GN ORFNames=MTCY253.04;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 16-402, AND FUNCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10629183; DOI=10.1128/jb.182.2.377-384.2000;
RA Wei J., Dahl J., Moulder J.W., Roberts E.A., O'Gaora P., Young D.B.,
RA Friedman R.L.;
RT "Identification of a Mycobacterium tuberculosis gene that enhances
RT mycobacterial survival in macrophages.";
RL J. Bacteriol. 182:377-384(2000).
RN [3]
RP PROTEIN SEQUENCE OF 2-7, AND SUBCELLULAR LOCATION.
RC STRAIN=H37Rv;
RX PubMed=11401966; DOI=10.1128/iai.69.7.4295-4302.2001;
RA Dahl J.L., Wei J., Moulder J.W., Laal S., Friedman R.L.;
RT "Subcellular localization of the intracellular survival-enhancing Eis
RT protein of Mycobacterium tuberculosis.";
RL Infect. Immun. 69:4295-4302(2001).
RN [4]
RP FUNCTION.
RC STRAIN=H37Rv;
RX PubMed=17449476; DOI=10.1074/jbc.c600280200;
RA Lella R.K., Sharma C.;
RT "Eis (enhanced intracellular survival) protein of Mycobacterium
RT tuberculosis disturbs the cross regulation of T-cells.";
RL J. Biol. Chem. 282:18671-18675(2007).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Ra, and H37Rv;
RX PubMed=17259625; DOI=10.1099/mic.0.2006/002642-0;
RA Samuel L.P., Song C.H., Wei J., Roberts E.A., Dahl J.L., Barry C.E. III,
RA Jo E.K., Friedman R.L.;
RT "Expression, production and release of the Eis protein by Mycobacterium
RT tuberculosis during infection of macrophages and its effect on cytokine
RT secretion.";
RL Microbiology 153:529-540(2007).
RN [6]
RP FUNCTION, ANTIBIOTIC RESISTANCE, ACETYLTRANSFERASE ACTIVITY ON
RP AMINOGLYCOSIDES, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19906990; DOI=10.1073/pnas.0907925106;
RA Zaunbrecher M.A., Sikes R.D. Jr., Metchock B., Shinnick T.M., Posey J.E.;
RT "Overexpression of the chromosomally encoded aminoglycoside
RT acetyltransferase eis confers kanamycin resistance in Mycobacterium
RT tuberculosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:20004-20009(2009).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DOMAIN.
RC STRAIN=H37Rv;
RX PubMed=21187903; DOI=10.1371/journal.ppat.1001230;
RA Shin D.M., Jeon B.Y., Lee H.M., Jin H.S., Yuk J.M., Song C.H., Lee S.H.,
RA Lee Z.W., Cho S.N., Kim J.M., Friedman R.L., Jo E.K.;
RT "Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell
RT death through redox-dependent signaling.";
RL PLoS Pathog. 6:E1001230-E1001230(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [9]
RP FUNCTION, ACETYLTRANSFERASE ACTIVITY ON CAPREOMYCIN, SUBSTRATE SPECIFICITY,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=23233486; DOI=10.1093/jac/dks497;
RA Houghton J.L., Green K.D., Pricer R.E., Mayhoub A.S., Garneau-Tsodikova S.;
RT "Unexpected N-acetylation of capreomycin by mycobacterial Eis enzymes.";
RL J. Antimicrob. Chemother. 68:800-805(2013).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH COENZYME A AND
RP ACETAMIDE, FUNCTION, ACETYLTRANSFERASE ACTIVITY ON AMINOGLYCOSIDES,
RP SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, DOMAIN,
RP REACTION MECHANISM, ACTIVE SITE, AND MUTAGENESIS OF HIS-119; TYR-126;
RP TRP-197; ASP-292; TYR-310 AND 400-PHE--PHE-402.
RC STRAIN=H37Rv;
RX PubMed=21628583; DOI=10.1073/pnas.1105379108;
RA Chen W., Biswas T., Porter V.R., Tsodikov O.V., Garneau-Tsodikova S.;
RT "Unusual regioversatility of acetyltransferase Eis, a cause of drug
RT resistance in XDR-TB.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:9804-9808(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH
RP ACETYL-COA, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP AND SUBUNIT.
RC STRAIN=H37Rv;
RX PubMed=22547814; DOI=10.1073/pnas.1120251109;
RA Kim K.H., An D.R., Song J., Yoon J.Y., Kim H.S., Yoon H.J., Im H.N.,
RA Kim J., Kim do J., Lee S.J., Kim K.H., Lee H.M., Kim H.J., Jo E.K.,
RA Lee J.Y., Suh S.W.;
RT "Mycobacterium tuberculosis Eis protein initiates suppression of host
RT immune responses by acetylation of DUSP16/MKP-7.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:7729-7734(2012).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF MUTANT ALA-204 IN COMPLEX WITH
RP COENZYME A AND TOBRAMYCIN, FUNCTION, ACETYLTRANSFERASE ACTIVITY ON
RP AMINOGLYCOSIDES, AND MUTAGENESIS OF CYS-204.
RX PubMed=24106131; DOI=10.1002/cbic.201300359;
RA Houghton J.L., Biswas T., Chen W., Tsodikov O.V., Garneau-Tsodikova S.;
RT "Chemical and structural insights into the regioversatility of the
RT aminoglycoside acetyltransferase Eis.";
RL ChemBioChem 14:2127-2135(2013).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF MUTANT ALA-204 IN COMPLEXES WITH
RP COENZYME A AND ISOTHIAZOLE S,S-DIOXIDE HETEROCYCLIC INHIBITORS, AND
RP ACTIVITY REGULATION.
RX PubMed=27010218; DOI=10.1021/acschembio.6b00110;
RA Willby M.J., Green K.D., Gajadeera C.S., Hou C., Tsodikov O.V., Posey J.E.,
RA Garneau-Tsodikova S.;
RT "Potent inhibitors of acetyltransferase Eis overcome kanamycin resistance
RT in Mycobacterium tuberculosis.";
RL ACS Chem. Biol. 11:1639-1646(2016).
CC -!- FUNCTION: Effector that is released into the host cell and affects host
CC immune responses; it negatively modulates inflammation, macrophage
CC autophagy, and cell death through redox-dependent signaling
CC (PubMed:17259625, PubMed:21187903). Acts as an acetyltransferase.
CC Acetylates 'Lys-55' of dual-specificity protein phosphatase 16
CC (DUSP16)/mitogen-activated protein kinase phosphatase-7 (MKP-7), a JNK-
CC specific phosphatase; this leads to the inhibition of JNK-dependent
CC autophagy, phagosome maturation, and ROS (reactive oxygen species)
CC generation for enhanced intracellular survival of M.tuberculosis
CC (PubMed:22547814). Inhibits Con A-mediated T-cell proliferation in
CC vitro (PubMed:17449476). Treatment of T-cells with Eis inhibits ERK1/2,
CC JAK pathway, and subsequent production of tumor necrosis factor-alpha
CC (TNF-alpha) and interleukin-4 (IL-4); on the contrary, there is
CC increased production of interferon-gamma (IFN-gamma) and interleukin-10
CC (IL-10), which indicates that immunity in response to Eis treatment is
CC skewed away from a protective T(H)1 response and Eis disturbs the cross
CC regulation of T-cells (PubMed:17449476). When expressed in M.smegmatis,
CC enhances intracellular survival of the bacteria in host macrophages
CC during infection (PubMed:10629183). {ECO:0000269|PubMed:10629183,
CC ECO:0000269|PubMed:17259625, ECO:0000269|PubMed:17449476,
CC ECO:0000269|PubMed:21187903, ECO:0000269|PubMed:22547814}.
CC -!- FUNCTION: Can also acetylate multiple amine groups of many
CC aminoglycoside (AG) antibiotics, leading to their inactivation, and
CC thus contributes to drug resistance (PubMed:19906990, PubMed:21628583,
CC PubMed:24106131). Is also able to acetylate and deactivate the cyclic
CC peptide antibiotic capreomycin, but not the other anti-tuberculous
CC drugs isoniazid and pyrazinamide (PubMed:23233486). Acetylates
CC kanamycin (KAN) more efficiently than amikacin (AMK), even though Eis
CC seems to bind AMK with higher affinity (PubMed:19906990). Does not
CC acetylate and inactivate streptomycin, apramycin and spectinomycin
CC (PubMed:19906990, PubMed:21628583). {ECO:0000269|PubMed:19906990,
CC ECO:0000269|PubMed:21628583, ECO:0000269|PubMed:23233486,
CC ECO:0000269|PubMed:24106131}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L-
CC lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752,
CC Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930;
CC Evidence={ECO:0000269|PubMed:22547814};
CC -!- ACTIVITY REGULATION: Is potently inhibited by several small-molecule
CC that share an isothiazole S,S-dioxide heterocyclic core. Some of these
CC inhibitors, when used in combination with KAN against resistant
CC M.tuberculosis, efficiently overcome Eis-mediated KAN resistance by
CC restoring the antibacterial activity of KAN.
CC {ECO:0000269|PubMed:27010218}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=112 uM for amikacin {ECO:0000269|PubMed:19906990};
CC KM=75 uM for amikacin (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:21628583};
CC KM=73 uM for amikacin (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:22547814};
CC KM=154 uM for kanamycin {ECO:0000269|PubMed:19906990};
CC KM=99 uM for kanamycin (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:21628583};
CC KM=81 uM for kanamycin A (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:22547814};
CC KM=178 uM for neamine (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:21628583};
CC KM=98 uM for neomycin B (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:21628583};
CC KM=48 uM for netilmicin (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:21628583};
CC KM=82 uM for paromomycin (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:21628583};
CC KM=85 uM for paromomycin (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:22547814};
CC KM=58 uM for sisomicin (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:21628583};
CC KM=63 uM for tobramycin (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:21628583};
CC KM=71 uM for tobramycin (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:22547814};
CC KM=654 uM for capreomycin (at 25 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:23233486};
CC Note=kcat is 0.020 sec(-1) with amikacin as substrate. kcat is 0.039
CC sec(-1) with kanamycin as substrate. kcat is 0.070 sec(-1) with
CC neamine as substrate. kcat is 0.130 sec(-1) with neomycin B as
CC substrate. kcat is 0.482 sec(-1) with netilmicin as substrate. kcat
CC is 0.058 sec(-1) with paromomycin as substrate. kcat is 0.270 sec(-1)
CC with sisomicin as substrate. kcat is 0.162 sec(-1) with tobramycin as
CC substrate (at 25 degrees Celsius and pH 8.0) (PubMed:21628583). kcat
CC is 0.017 sec(-1) with amikacin as substrate. kcat is 0.032 sec(-1)
CC with kanamycin A as substrate. kcat is 0.032 sec(-1) with paromomycin
CC as substrate. kcat is 0.179 sec(-1) with tobramycin as substrate (at
CC 25 degrees Celsius and pH 8.0) (PubMed:22547814). kcat is 1.25 sec(-
CC 1) with capreomycin as substrate (at 25 degrees Celsius and pH 8.0)
CC (PubMed:23233486). Catalytic efficiency is 3-fold higher for
CC acetylation of kanamycin than for acetylation of amikacin
CC (PubMed:19906990). {ECO:0000269|PubMed:19906990,
CC ECO:0000269|PubMed:21628583, ECO:0000269|PubMed:22547814};
CC -!- SUBUNIT: Homohexamer; trimer of dimers. {ECO:0000269|PubMed:21628583,
CC ECO:0000269|PubMed:22547814}.
CC -!- INTERACTION:
CC P9WFK7; P9WFK7: eis; NbExp=2; IntAct=EBI-15929122, EBI-15929122;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11401966}. Host
CC cytoplasmic vesicle, host phagosome {ECO:0000269|PubMed:17259625}.
CC Extracellular vesicle, bacterial extracellular vesicle
CC {ECO:0000269|PubMed:17259625}. Host extracellular space
CC {ECO:0000269|PubMed:17259625}. Note=Eis is present in the macrophage
CC cytoplasm from 4 to 96 hours post-infection.
CC {ECO:0000269|PubMed:17259625}.
CC -!- DOMAIN: The Eis monomer consists of three regions that are assembled
CC into a heart-shaped molecule (PubMed:21628583). This shape is formed by
CC an unusual fusion of two general control non-derepressible 5 (GCN5)-
CC related N-acetyltransferase (GNAT) regions and a C-terminal region
CC (PubMed:21628583). The N-acetyltransferase domain of Eis is responsible
CC for its modulation of ROS generation and pro-inflammatory responses in
CC macrophages (PubMed:21187903). {ECO:0000269|PubMed:21187903,
CC ECO:0000269|PubMed:21628583}.
CC -!- DISRUPTION PHENOTYPE: No significant difference in terms of
CC intracellular survival in U-397 macrophages and in an in vivo mouse
CC aerosol model of infection (PubMed:17259625). A strain lacking this
CC gene induces more TNF-alpha but less IL-10 production in primary human
CC monocytes than wild-type (PubMed:17259625). Macrophages infected with a
CC M.tuberculosis eis-deletion mutant display markedly increased
CC accumulation of massive autophagic vacuoles and formation of
CC autophagosomes in vitro and in vivo (PubMed:21187903). Infection of
CC macrophages with this mutant increases the production of tumor necrosis
CC factor-alpha and interleukin-6 over the levels produced by infection
CC with wild-type or complemented strains (PubMed:21187903). Elevated ROS
CC generation in macrophages infected with this mutant (for which NADPH
CC oxidase and mitochondria are largely responsible) render the cells
CC highly sensitive to autophagy activation and cytokine production;
CC despite considerable activation of autophagy and pro-inflammatory
CC responses, these infected macrophages undergo caspase-independent cell
CC death (PubMed:21187903). {ECO:0000269|PubMed:17259625,
CC ECO:0000269|PubMed:21187903}.
CC -!- MISCELLANEOUS: Increased expression of eis due to point mutations in
CC the promoter region of eis is responsible for resistance to the second-
CC line injectable drug kanamycin in a number of M.tuberculosis clinical
CC isolates, through acetylation of its amino groups, which leads to
CC inactivation of the drug. {ECO:0000269|PubMed:19906990}.
CC -!- SIMILARITY: Belongs to the acetyltransferase Eis family.
CC {ECO:0000255|HAMAP-Rule:MF_01812}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF03768.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL123456; CCP45207.1; -; Genomic_DNA.
DR EMBL; AF144099; AAF03768.1; ALT_INIT; Genomic_DNA.
DR PIR; C70685; C70685.
DR RefSeq; NP_216932.2; NC_000962.3.
DR RefSeq; WP_003903886.1; NC_000962.3.
DR PDB; 3R1K; X-ray; 1.95 A; A=1-402.
DR PDB; 3RYO; X-ray; 2.80 A; A/B/C/D/E/F/G/H/I/J/K/L=1-402.
DR PDB; 3SXO; X-ray; 2.50 A; A/B=1-402.
DR PDB; 3UY5; X-ray; 2.50 A; A=1-402.
DR PDB; 4JD6; X-ray; 3.50 A; A/B/C/D/E/F=1-402.
DR PDB; 5EBV; X-ray; 2.20 A; A=2-402.
DR PDB; 5EC4; X-ray; 2.21 A; A=2-402.
DR PDB; 5IV0; X-ray; 2.10 A; A=1-402.
DR PDB; 5TVJ; X-ray; 2.30 A; A=2-402.
DR PDB; 6B0U; X-ray; 2.80 A; A/B/C=1-402.
DR PDB; 6B3T; X-ray; 2.40 A; A=1-402.
DR PDB; 6P3T; X-ray; 2.50 A; A=1-402.
DR PDB; 6P3U; X-ray; 2.55 A; A=1-402.
DR PDB; 6P3V; X-ray; 2.50 A; A=1-402.
DR PDB; 6VUR; X-ray; 2.20 A; A=1-402.
DR PDB; 6VUS; X-ray; 2.28 A; A=1-402.
DR PDB; 6VUT; X-ray; 2.73 A; A=1-402.
DR PDB; 6VUU; X-ray; 2.60 A; A=1-402.
DR PDB; 6VUW; X-ray; 2.87 A; A=1-402.
DR PDB; 6VUX; X-ray; 1.97 A; A=1-402.
DR PDB; 6VUY; X-ray; 2.70 A; A=1-402.
DR PDB; 6VUZ; X-ray; 2.65 A; A=1-402.
DR PDB; 6VV0; X-ray; 3.00 A; A=1-402.
DR PDB; 6VV1; X-ray; 2.45 A; A=1-402.
DR PDB; 6VV2; X-ray; 2.95 A; A=1-402.
DR PDB; 6VV3; X-ray; 2.40 A; A=1-402.
DR PDB; 6X10; X-ray; 2.03 A; A=1-402.
DR PDB; 6X6G; X-ray; 2.15 A; AAA=1-402.
DR PDB; 6X6I; X-ray; 1.90 A; AAA=1-402.
DR PDB; 6X6Y; X-ray; 2.50 A; AAA=1-402.
DR PDB; 6X7A; X-ray; 2.08 A; AAA=1-402.
DR PDBsum; 3R1K; -.
DR PDBsum; 3RYO; -.
DR PDBsum; 3SXO; -.
DR PDBsum; 3UY5; -.
DR PDBsum; 4JD6; -.
DR PDBsum; 5EBV; -.
DR PDBsum; 5EC4; -.
DR PDBsum; 5IV0; -.
DR PDBsum; 5TVJ; -.
DR PDBsum; 6B0U; -.
DR PDBsum; 6B3T; -.
DR PDBsum; 6P3T; -.
DR PDBsum; 6P3U; -.
DR PDBsum; 6P3V; -.
DR PDBsum; 6VUR; -.
DR PDBsum; 6VUS; -.
DR PDBsum; 6VUT; -.
DR PDBsum; 6VUU; -.
DR PDBsum; 6VUW; -.
DR PDBsum; 6VUX; -.
DR PDBsum; 6VUY; -.
DR PDBsum; 6VUZ; -.
DR PDBsum; 6VV0; -.
DR PDBsum; 6VV1; -.
DR PDBsum; 6VV2; -.
DR PDBsum; 6VV3; -.
DR PDBsum; 6X10; -.
DR PDBsum; 6X6G; -.
DR PDBsum; 6X6I; -.
DR PDBsum; 6X6Y; -.
DR PDBsum; 6X7A; -.
DR AlphaFoldDB; P9WFK7; -.
DR SMR; P9WFK7; -.
DR STRING; 83332.Rv2416c; -.
DR BindingDB; P9WFK7; -.
DR ChEMBL; CHEMBL3879870; -.
DR PaxDb; P9WFK7; -.
DR DNASU; 885903; -.
DR GeneID; 885903; -.
DR KEGG; mtu:Rv2416c; -.
DR PATRIC; fig|83332.12.peg.2706; -.
DR TubercuList; Rv2416c; -.
DR eggNOG; COG4552; Bacteria.
DR BRENDA; 2.3.1.81; 3445.
DR BRENDA; 2.3.1.87; 3445.
DR Reactome; R-HSA-9636569; Suppression of autophagy.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0097691; C:bacterial extracellular vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0044161; C:host cell cytoplasmic vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0043655; C:host extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0034069; F:aminoglycoside N-acetyltransferase activity; IDA:MTBBASE.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008080; F:N-acetyltransferase activity; TAS:Reactome.
DR GO; GO:0030649; P:aminoglycoside antibiotic catabolic process; IMP:MTBBASE.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR GO; GO:0033661; P:effector-mediated defense to host-produced reactive oxygen species; IDA:GO_Central.
DR GO; GO:0052032; P:modulation by symbiont of host inflammatory response; IDA:GO_Central.
DR GO; GO:0052167; P:modulation by symbiont of host innate immune response; IDA:MTBBASE.
DR GO; GO:0052040; P:modulation by symbiont of host programmed cell death; IDA:MTBBASE.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR GO; GO:0034054; P:suppression by symbiont of host defense-related programmed cell death; TAS:Reactome.
DR Gene3D; 3.30.1050.10; -; 1.
DR HAMAP; MF_01812; Eis; 1.
DR InterPro; IPR041380; Acetyltransf_17.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR025559; Eis_dom.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR022902; NAcTrfase_Eis.
DR InterPro; IPR036527; SCP2_sterol-bd_dom_sf.
DR Pfam; PF17668; Acetyltransf_17; 1.
DR Pfam; PF13530; SCP2_2; 1.
DR SUPFAM; SSF55718; SSF55718; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Antibiotic resistance;
KW Direct protein sequencing; Host cytoplasmic vesicle; Reference proteome;
KW Secreted; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:11401966"
FT CHAIN 2..402
FT /note="N-acetyltransferase Eis"
FT /id="PRO_0000220262"
FT DOMAIN 3..154
FT /note="N-acetyltransferase"
FT ACT_SITE 126
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:21628583"
FT ACT_SITE 402
FT /note="Proton acceptor; via carboxylate"
FT /evidence="ECO:0000305|PubMed:21628583"
FT BINDING 85..87
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:22547814,
FT ECO:0000305|PubMed:21628583, ECO:0007744|PDB:3RYO"
FT BINDING 93..98
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:22547814,
FT ECO:0000305|PubMed:21628583, ECO:0000305|PubMed:24106131,
FT ECO:0000305|PubMed:27010218, ECO:0007744|PDB:3RYO"
FT BINDING 121..122
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:22547814,
FT ECO:0000305|PubMed:21628583, ECO:0007744|PDB:3RYO"
FT MUTAGEN 119
FT /note="H->A: Decreases catalytic activity on AG substrates,
FT leads to a change in the number of acetylated sites."
FT /evidence="ECO:0000269|PubMed:21628583"
FT MUTAGEN 126
FT /note="Y->A: Abolishes catalytic activity on AG
FT substrates."
FT /evidence="ECO:0000269|PubMed:21628583"
FT MUTAGEN 197
FT /note="W->A: Abolishes catalytic activity on AG
FT substrates."
FT /evidence="ECO:0000269|PubMed:21628583"
FT MUTAGEN 204
FT /note="C->A: No effect on catalytic activity on AG
FT substrates. Prevents artifactual CoA adduct formation
FT during crystallization."
FT /evidence="ECO:0000269|PubMed:24106131"
FT MUTAGEN 292
FT /note="D->A: Nearly abolishes catalytic activity on AG
FT substrates."
FT /evidence="ECO:0000269|PubMed:21628583"
FT MUTAGEN 310
FT /note="Y->A: Nearly abolishes catalytic activity on AG
FT substrates."
FT /evidence="ECO:0000269|PubMed:21628583"
FT MUTAGEN 400..402
FT /note="Missing: Nearly abolishes catalytic activity on AG
FT substrates."
FT /evidence="ECO:0000269|PubMed:21628583"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 10..12
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 13..23
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:5EC4"
FT HELIX 30..36
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 58..71
FT /evidence="ECO:0007829|PDB:3R1K"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 75..87
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:6VUX"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 96..110
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 114..119
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 121..126
FT /evidence="ECO:0007829|PDB:6P3V"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 136..143
FT /evidence="ECO:0007829|PDB:3R1K"
FT TURN 144..146
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 172..185
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 194..202
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:6VUZ"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 222..228
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 235..245
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 246..257
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 263..269
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:5EC4"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 285..292
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 294..300
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 301..307
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 317..323
FT /evidence="ECO:0007829|PDB:3R1K"
FT TURN 324..326
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 327..334
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 337..342
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 348..351
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 353..360
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 362..364
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 366..371
FT /evidence="ECO:0007829|PDB:3R1K"
FT STRAND 374..378
FT /evidence="ECO:0007829|PDB:3R1K"
FT HELIX 380..390
FT /evidence="ECO:0007829|PDB:3R1K"
SQ SEQUENCE 402 AA; 43804 MW; EF06F75C00F05333 CRC64;
MTVTLCSPTE DDWPGMFLLA AASFTDFIGP ESATAWRTLV PTDGAVVVRD GAGPGSEVVG
MALYMDLRLT VPGEVVLPTA GLSFVAVAPT HRRRGLLRAM CAELHRRIAD SGYPVAALHA
SEGGIYGRFG YGPATTLHEL TVDRRFARFH ADAPGGGLGG SSVRLVRPTE HRGEFEAIYE
RWRQQVPGGL LRPQVLWDEL LAECKAAPGG DRESFALLHP DGYALYRVDR TDLKLARVSE
LRAVTADAHC ALWRALIGLD SMERISIITH PQDPLPHLLT DTRLARTTWR QDGLWLRIMN
VPAALEARGY AHEVGEFSTV LEVSDGGRFA LKIGDGRARC TPTDAAAEIE MDRDVLGSLY
LGAHRASTLA AANRLRTKDS QLLRRLDAAF ASDVPVQTAF EF
